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Hiroyuki Okada

Publications and source records attributed to Hiroyuki Okada.

At least 19 recordsLinked to original sources
PubMed2006

Microglial cell line established from prion protein-overexpressing mice is susceptible to various murine prion strains.

Several lines of evidence suggest that microglia have important roles in the pathogenesis of prion diseases. Here, we establish a novel microglial cell line (MG20) from neonatal tga20 mice that overexpress murine prion protein. After exposure to Chandler scrapie, we observed the replication and accumulation of disease-associated forms of the prion protein in MG20 cells up to the 15th passage. Furthermore, MG20 cells were susceptible to ME7, Obihiro scrapie, and bovine spongiform encephalopathy agents. Thus, MG20 cell lines persistently infected with various murine prion strains provide a useful model for the study of the pathogenesis of prion diseases.

Animals↗
PubMed2006

Changes in cerebral blood flow under the prone condition with and without massage.

To investigate changes in regional cerebral blood flow (rCBF) under the prone condition with and without light massage on the back, we measured rCBF quantitatively in healthy human subjects using positron emission tomography with H(2)15O. Biochemical tests showed that the light massage (palm-pressure) reduced levels of stress-related serum cortisol and salivary stress protein chromogranin-A measured after the PET examination. Absolute rCBF significantly increased in the parietal cortex (precuneus) under the prone condition compared with the supine condition, and this rCBF increase was in parallel with comfortable sensation and slowing heart rate during the massage. Correlation analysis in statistical parametric mapping showed that the amygdalar and basal forebrain rCBF correlated with parasympathetic function (heart rate reduction), indicating involvement of the forebrain-amygdala system in mediating activities in the autonomic nervous system in the presence of comfortable sensation. To conclude, prone posture itself can stimulate the precuneus region to raise awareness, and the light massage on the back may help accommodate the brain to comfortable stimulation.

Adult↗
PubMed2006

Endocrine disruptor bisphenol A strongly binds to human estrogen-related receptor gamma (ERRgamma) with high constitutive activity.

Bisphenol A (BPA) has been acknowledged as an estrogenic chemical able to interact with human estrogen receptors (ER). Many lines of evidence reveal that BPA has an impact as an endocrine disruptor even at low doses. However, its binding to ER and hormonal activity is extremely weak, making the intrinsic significance of low dose effects obscure. We thus supposed that BPA might interact with nuclear receptor(s) other than ER. Here we show that BPA strongly binds to human estrogen-related receptor gamma (ERRgamma), an orphan receptor and one of 48 human nuclear receptors. In a binding assay using [3H]4-hydroxytamoxifen (4-OHT) as a tracer, BPA exhibited a definite dose-dependent receptor binding curve with the IC50 value of 13.1 nM. 4-Nonylphenol and diethylstilbestrol were considerably weaker (5-50-fold less than BPA). When examined in the reporter gene assay for ERRgamma using HeLa cells, BPA completely preserved ERRgamma's high constitutive activity. Notably, BPA exhibited a distinct antagonist action to reverse the inverse agonist activity of 4-OHT, retaining high basal activity. ERRgamma is expressed in a tissue-restricted manner, for example very strongly in the mammalian brain during development, and in the adult in the brain, lung and other tissues. It will now be important to evaluate whether BPA's hitherto reported low dose effects may be mediated through ERRgamma.

Benzhydryl Compounds↗
PubMed2006

[Measurement of radiation exposure to a PET institution driver from patients injected with FDG].

With the recent increase in FDG-PET examinations, concern has mounted regarding radiation exposure to hospital staff and the general public from patients injected with FDG. Because our PET institution is located 15 km from the hospital that provides these examinations, a driver has been designated to transport patients injected with FDG. This study was designed to measure the radiation dose to the driver from these patients (n=28) and to compare it with the estimated dose. A pocket dosimeter was used to measure radiation exposure to the driver. When the distances between the driver and patient were 1.1 m and 1.9 m, mean measured doses were 7.31 microSv and 2.26 microSv, respectively, while mean estimated doses were 8.61 microSv and 2.82 microSv, respectively, per trip. It was presumed that maximum radiation exposure per year was between 3.02 mSv (1.1 m) and 0.92 mSv (1.9 m). According to our data, the measured dose was 20% lower than the estimated dose. This discrepancy may be due to the difference between the volume source (measured dose) and point source (estimated dose).

Automobiles↗
PubMed2006

Localization and secretion of epidermal growth factor in the parotid gland and its intragastric kinetics in sheep.

Ruminants secrete a large quantity of saliva that is rich in electrolytes; however, it remains unclear whether their parotid saliva contains epidermal growth factor (EGF). The present study was set up to examine the distribution of EGF and transforming growth factor-alpha (TGF-alpha) in the ovine parotid and submandibular glands and the salivary secretion of EGF-like binding activity (EGF-LBA) as the sum of EGF and TGF-alpha in conscious sheep. We also measured changes in the intragastric concentration of EGF-LBA in the ovine rumen and abomasum, and examined the effect of bilateral diversion of parotid saliva on intragastric EGF-LBA concentration in sheep. Both the ovine parotid and, to a lesser extent, the submandibular glands contained EGF-LBA. Immunohistochemical study showed that EGF and TGF-alpha-immunoreactivities were localized in the ductal epithelium in both glands. Transcriptional expression of EGF and TGF-alpha mRNA was demonstrated in both glands by reverse transcription-polymerase chain reaction (RT-PCR). In conscious sheep, the parotid gland continuously secreted EGF-LBA in the saliva before feeding, and the secretion of parotid EGF-LBA was markedly increased during feeding. After diversion of the parotid saliva for 1 week, EGF-LBA concentration in the ruminal fluid, but not in the abomasal fluid, decreased in the postprandial period, indicating that parotid EGF-LBA is a primary source of EGF-LBA for the rumen fluid during the postprandial period in sheep. Moreover, RT-PCR detected the expression of TGF-alpha mRNA in the rumen and abomasum and that of EGF in the abomasum, implying that these stomachs possibly supply, in part, EGF-LBA to the luminal fluid.

Abomasum↗
PubMed2006

Utility of gallium-67 scintigraphy for evaluation of cardiac sarcoidosis with ventricular tachycardia.

BACKGROUND: The outcome of cardiac sarcoidosis is sometimes very poor. Ventricular tachycardia (VT) associated with cardiac sarcoidosis is the most common cause of sudden death among most patients. However, there is no established method for potential VT in patients with cardiac sarcoidosis. Thus, we investigated the utility of evaluation of gallium-67 scintigraphy for potential VT in patients with cardiac sarcoidosis. METHODS AND RESULTS: Cardiac sarcoidosis was diagnosed in 25 patients at ours or collaborating hospitals during the period 1982 through 2004. Twenty-one of these patients were treated with corticosteroid, and these patients were divided into two groups, depending on whether VT was present: a non-VT group (n=7) and a VT group (n=14). Laboratory and gallium-67 scintigraphy findings were examined in both groups. During the follow-up period, initial and maintenance dosages of corticosteroid did not differ significantly between the groups. Accumulation of gallium-67 in the heart at the time of diagnosis was detected more frequently in the VT group than in the non-VT group (14.3 vs. 71.4%, p<0.05). Six of the seven VT patients who underwent follow-up examination showed improvement on the scintigram obtained after treatment. Five of the six showed no VT recurrence in terms of Holter electrocardiogram, electrophysiologic study, or delivery of implantable cardioverter defibrillator shock. Serum angiotensin-converting enzyme and lysozyme concentrations were within normal limits in most patients in both groups. CONCLUSIONS: Activity of sarcoid granulomas may be associated with the occurrence of VT. Gallium-67 scintigraphy reflects the activity of sarcoid granulomas and thus is useful for evaluation of cardiac sarcoidosis in patients with potential VT.

Adrenal Cortex Hormones↗
PubMed2006

Brain serotonin transporter density and aggression in abstinent methamphetamine abusers.

CONTEXT: In animals, methamphetamine is known to have a neurotoxic effect on serotonin neurons, which have been implicated in the regulation of mood, anxiety, and aggression. It remains unknown whether methamphetamine damages serotonin neurons in humans. OBJECTIVE: To investigate the status of brain serotonin neurons and their possible relationship with clinical characteristics in currently abstinent methamphetamine abusers. DESIGN: Case-control analysis. SETTING: A hospital research center. PARTICIPANTS: Twelve currently abstinent former methamphetamine abusers (5 women and 7 men) and 12 age-, sex-, and education-matched control subjects recruited from the community. INTERVENTIONS: The brain regional density of the serotonin transporter, a structural component of serotonin neurons, was estimated using positron emission tomography and trans-1,2,3,5,6,10-beta-hexahydro-6-[4-(methylthio)phenyl]pyrrolo-[2,1-a]isoquinoline ([(11)C](+)McN-5652). Estimates were derived from region-of-interest and statistical parametric mapping methods, followed by within-case analysis using the measures of clinical variables. MAIN OUTCOME MEASURES: The duration of methamphetamine use, the magnitude of aggression and depressive symptoms, and changes in serotonin transporter density represented by the [(11)C](+)McN-5652 distribution volume. RESULTS: Methamphetamine abusers showed increased levels of aggression compared with controls. Region-of-interest and statistical parametric mapping analyses revealed that the serotonin transporter density in global brain regions (eg, the midbrain, thalamus, caudate, putamen, cerebral cortex, and cerebellum) was significantly lower in methamphetamine abusers than in control subjects, and this reduction was significantly inversely correlated with the duration of methamphetamine use. Furthermore, statistical parametric mapping analyses indicated that the density in the orbitofrontal, temporal, and anterior cingulate areas was closely associated with the magnitude of aggression in methamphetamine abusers. CONCLUSIONS: Protracted abuse of methamphetamine may reduce the density of the serotonin transporter in the brain, leading to elevated aggression, even in currently abstinent abusers.

Adult↗
PubMed2006

Risk factors and indications for colectomy in ulcerative colitis patients are different according to patient's clinical background.

PURPOSE: Despite progress in medical treatment for ulcerative colitis, a considerable fraction of ulcerative colitis patients undergo colectomy. We analyzed the clinical variables of ulcerative colitis patients and determined the risk factors and indications for colectomy. METHODS: The clinical records of 981 consecutive Japanese patients with ulcerative colitis were reviewed both retrospectively and prospectively. RESULTS: Of 981 patients with ulcerative colitis, 85 patients underwent colectomy. Multivariate analysis indicated that male gender (risk ratio, 2.16; 95 percent confidence interval, 1.37-3.42), onset year during and after 2000 (risk ratio, 2.85; 95 percent confidence interval, 1.31-6.22), severe disease activity (risk ratio, 2; 95 percent confidence interval, 1.15-3.48), corticosteroid resistance (risk ratio, 7.05; 95 percent confidence interval, 4.29-11.59), and complications because of corticosteroid administration (risk ratio, 3.55; 95 percent confidence interval, 2.08-6.06) were significant risk factors for colectomy. In patients with disease duration of more than five years, only corticosteroid resistance and complications because of corticosteroid were significant risk factors for colectomy. When we stratified indications for colectomy for the 85 cases via patient disease duration, massive hemorrhage was a relatively frequent cause of colectomy in patients with a disease duration of less than five years (P = 0.091). On the other hand, colon dysplasia or cancer was a major cause for colectomy in patients with a disease duration of more than ten years (P = 0.0001). CONCLUSIONS: In ulcerative colitis patients, the risk factors and indications for colectomy were different according to the patient's clinical background. Our findings may help to predict patients with ulcerative colitis who have a high risk for colectomy.

Adrenal Cortex Hormones↗
PubMed2006

FDG PET for the assessment of myometrial infiltration in clinical stage I uterine corpus cancer.

OBJECTIVE: For surgical planning of uterine corpus cancer, prior knowledge of the depth of myometrial invasion is important. Curative tumour resection is possible in superficial invasion (stages IA and IB), while post-surgical chemotherapy or radiation therapy is required in deep invasion (stage IC). We evaluated the value of positron emission tomography with 2-[(18)F]fluoro-2-deoxy-D-glucose (FDG PET) for estimating the myometrial invasion in uterine corpus cancer. METHODS: We studied 22 patients with clinical stage I uterine corpus cancer, who underwent FDG PET prior to surgery. Standardized uptake value (SUV; tracer activity per injected dose normalized to body weight) was calculated on the PET image. PET findings were compared with magnetic resonance imaging (MRI) and the surgical staging. RESULTS: The surgical stage was IA in five, IB in 11 and IC in six patients. SUVs in deep invasion (15.69+/-4.73, 8.83-21.84) were significantly higher than those in superficial invasion (9.09+/-3.29, 2.68-15.41) (P<0.005). Using 12.0 as a cut-off value of SUV for the differentiation of these two groups, PET results were correct in 19 patients but were incorrect in three patients. Although both PET and MRI provided correct staging in 14 patients, only MRI overestimated the myometrial invasion in four patients with stage IB and showed inconclusive findings in one patient with stage IC. Four of these five patients were post-menopausal. CONCLUSIONS: The cut-off value of SUV (=12.0) may be a useful index for the differentiation of superficial invasion and deep invasion. FDG PET may be feasible for predicting the myometrial infiltration of uterine corpus cancer, especially when uterine atrophy makes it difficult at MRI in post-menopausal patients.

Adult↗
PubMed2006

Endoscopic therapy for bleeding esophageal varices improves the outcome of Child C cirrhotic patients.

BACKGROUND AND AIM: Bleeding from esophageal varices is one of the frequent severe complications arising in patients with liver cirrhosis. The management of esophageal varices is therefore important for patient survival. The purpose of this study was to clarify the predictive factors for mortality in patients with Child C cirrhosis presenting with variceal bleeding. METHODS: A retrospective analysis of 77 Child C cirrhotic patients with bleeding from esophageal varices was conducted. All patients received endoscopic therapy. Twenty-nine patients received endoscopic variceal ligation, and 48 patients received endoscopic injection sclerotherapy or endoscopic injection sclerotherapy with ligation. Univariate and multivariate analyses of clinical data were performed to identify the prognostic factors for survival for these 77 patients. RESULTS: Fifty-seven of 77 patients received endoscopic therapy within 24 h after variceal bleeding, and bleeding was controlled in 55 (96.5%). The remaining 20 patients received endoscopic therapy more than 24 h after bleeding. Higher bilirubin level and rebleeding were the predictive parameters for 6-week survival in the 77 patients, according to univariate and multivariate analysis. Higher bilirubin level, refractory ascites, and the presence of hepatocellular carcinoma were the predictive parameters for mortality in 77 patients as determined by multivariate analysis. CONCLUSIONS: Endoscopic therapy was effective in controlling acute variceal bleeding of Child C cirrhotic patients. The prognosis of Child C stage patients presenting with variceal bleeding depended on the severity of liver damage and the presence of hepatocellular carcinoma.

Carcinoma, Hepatocellular↗
PubMed2006

Centrifugal leukocytapheresis therapy for ulcerative colitis without concurrent corticosteroid administration.

Corticosteroid administration is an important therapy for active ulcerative colitis. However, long-term corticosteroid use is associated with serious complications such as osteoporosis, diabetes, and growth retardation. The effect of combination therapy corticosteroid plus leukocytapheresis has been previously reported, but that of leukocytapheresis with no corticosteroid is unknown. We carried out a preliminary study of six patients (two men and four women) with active ulcerative colitis (severe in two, moderately severe in four) who did not respond to 5-aminosalicylate derivatives, but refused corticosteroid use. Centrifugal leukocytapheresis was carried out once per week totaling four sessions per course. Treatment was considered effective when patients experienced clinical remission, which was defined as a frequency of diarrhea of four times or less and absence of visible blood in the stool, after one course. Leukocytapheresis was effective in five of six patients(83%). With cases stratified by severity, both severe cases and three of four moderately severe cases showed effectiveness. Clinical activity scores according to Lichtiger et al. in cases where leukocytapheresis was effective decreased from 9.8 to 6.6 at 1 week (P < 0.0001), declining further 2.4 at the end of the course. No obvious complications of leukocytapheresis were noted except for a decrease in hemoglobin by 1 g/dL. Centrifugal leukocytapheresis without corticosteroid treatment can induce remission in patients with active ulcerative colitis, and might be particularly beneficial for patients in whom adverse effects preclude the use of corticosteroids.

Adolescent↗
PubMed2005

Cerebral hemodynamics evaluation by near-infrared time-resolved spectroscopy: correlation with simultaneous positron emission tomography measurements.

We compared pharmacologically-perturbed hemodynamic parameters (cerebral blood volume; CBV, and flow; CBF) by acetazolamide administration in six healthy human subjects studied with positron emission tomography (PET) and near-infrared (NIR) time-resolved spectroscopy (TRS) simultaneously to investigate whether NIR-TRS could measure in vivo hemodynamics in the brain tissue quantitatively. Simultaneously with the PET measurements, TRS measurements were performed at the forehead with four different optode spacing from 2 cm to 5 cm. Total hemoglobin and oxygen saturation (SO2) measured by TRS significantly increased after administration of acetazolamide at any optode spacing in all subjects. In PET study, CBV and CBF were estimated in the following three volumes of interest (VOIs) determined on magnetic resonance images, VOI1: scalp and skull, VOI2: gray matter region, VOI3: gray and white matter regions. Acetazolamide treatment elevated CBF and CBV significantly in VOI2 and VOI3 but VOI1. TRS-derived CBV was more strongly correlated with PET-derived counterpart in VOI2 and VOI3 when the optode spacing was above 4 cm, although optical signal from cerebral tissue could be caught with any optode spacing. As to increase of the CBV, 4 cm of optode spacing correlated best with VOI2. To support the result of TRS-PET experiment, we also estimated the contribution ratios of intracerebral tissue to observed absorption change based on diffusion theory. The contribution ratios at 4 cm were estimated as follows: 761 nm: 50%, 791 nm: 72%, 836 nm: 70%. These results demonstrated that NIR-TRS with 4 cm of optode spacing could measure cerebral hemodynamic responses optimally and quantitatively.

Acetazolamide↗
PubMed2005

Orthostatic posture affects brain hemodynamics and metabolism in cerebrovascular disease patients with and without coronary artery disease: a positron emission tomography study.

To investigate whether a physiological change in the orthostatic condition is associated with a deterioration of cerebrovascular and metabolic homeostasis in patients with neurocardiovascular compromises, we examined 10 patients with unilateral carotid artery occlusive disease (CVD), 6 CVD patients with coronary artery disease (CVDC), and 10 healthy subjects scanned twice under supine and sitting conditions by positron emission tomography (PET). Repeated measures analysis of variance showed significant reductions in regional cerebral blood flow (rCBF) and cerebral oxygen metabolism (rCMRO2) and tendency of increase in oxygen extraction fraction (OEF) in the affected-side parietal cortex during assuming of upright posture in the CVDC group, and there was a significant OEF increase to maintain rCMRO2 constant during sitting in the CVD counterpart. In this ischemic region, there were negative correlations between changes in OEF and rCBF in the CVD (P < 0.05) and CVDC groups (P < 0.01). Postural reductions in rCBF and CMRO2 in the parietal region were significantly greater in the CVDC group than those in the CVD group. While rCBF remained constant with mean arterial blood pressure (MABP) in healthy subjects, an rCBF reduction was found in the affected parietal cortex in proportion to the upright posture-induced MABP decrease in the CVDC group. These results indicate that patients suffering from both cerebral and coronary artery diseases may be at greater risk of deterioration of local perfusion pressure and metabolic regulation in the hemodynamically susceptible brain region during upright posture.

Aged↗
PubMed2005

HLA-DQA1*0103-DQB1*0601 haplotype and Helicobacter pylori-positive gastric mucosa-associated lymphoid tissue lymphoma.

BACKGROUND & AIMS: Immune responses to Helicobacter pylori are important in the pathogenesis of gastric mucosa-associated lymphoid tissue (MALT) lymphoma. In this retrospective case study, we investigated whether certain alleles and haplotypes of major histocompatibility complex genes are associated with gastric MALT lymphoma and the efficacy of H pylori eradication therapy on the lymphoma. METHODS: Blood samples were obtained from 18 patients with H pylori-positive gastric MALT lymphoma (5 men and 13 women; age range, 51-80 years), 30 patients with H pylori-positive non-ulcer dyspepsia (17 men and 13 women; age range, 37-77 years), and 30 patients with H pylori-negative non-ulcer dyspepsia (12 men and 18 women; age range, 37-77 years). HLA-DQA1 and DQB1 allele typing was performed by use of a polymerase chain reaction sequence-specific oligonucleotide procedure. All patients with MALT lymphoma were treated with H pylori eradication therapy and followed up by repeated endoscopy and biopsy. RESULTS: We found a significant increase in alleles HLA-DQA1*0103 and HLA-DQB1*0601, and a haplotype DQA1*0103-DQB1*0601, in MALT lymphoma patients when compared with non-ulcer dyspepsia patients who were either H pylori-positive or not and with a healthy control population. After H pylori eradication, the lymphomas regressed completely in all 10 patients who possessed the DQA1*0103-DQB1*0601 haplotype but in only 4 of the 8 without this haplotype (P = .023). CONCLUSIONS: DQA1*0103-DQB1*0601 haplotype-positive gastric MALT lymphoma is likely to respond to therapy by eradication of H pylori.

Adult↗